"Run It!" was generally well received by music critics; many praised Brown's vocals and Scott Storch's production. Commercially, the song was successful, peaking inside the top ten in six countries and the top twenty in four. The song also managed to top the charts in the United States, Australia and New Zealand. The music video earned nominations at the 2006 MTV Video Music Awards for "Best New Artist" and "Viewer's Choice".
Bill Lamb of About.com awarded "Run It" a four star rating, commending the song's backing music, Brown's voice, and chorus but called it "another cookie cutter Scott Storch production." Andy Kellman of Allmusic noted it as one of the album's top tracks, commenting that the song's "way of tempering Brown's small-town innocence with hard-edged backing and a guest spot from an MC of ill repute is clearly a strategy to make the singer appeal to more than tween girls." Christian Hoard of Rolling Stone said that the song gets by "thanks to a slinky synth beat and the mix of smooth seduction and cunning come-ons in Brown's baby-mack vocals."
"Run It!" debuted at No. 92 on the Billboard Hot 100 in the issue dated August 27, 2005. After eight weeks on the chart, the song entered the top ten at number eight on October 22, 2005, receiving the airplay gainer title. It gained the airplay title again in the following week, climbing to number two on the chart, where it stalled for a month. On November 26, 2005, "Run It!" peaked on the Billboard Hot 100 at number one, becoming Brown's first number one single on the chart. That same week, the song was also at the top of the US Hot R&B/Hip-Hop Songs and the US Radio Songs. Two weeks later, it topped the US Pop Songs chart. The song remained on top of the Hot 100 for five weeks, becoming his longest lasting number one single on the chart. It was certified platinum by the Recording Industry Association of America (RIAA) for shipments of one million copies.
"Run It!" debuted and peaked at number one on the Australian Singles Chart in the issue dated January 29, 2006. The song remained at the top of the chart for three non-consecutive weeks and exited after fifteen weeks. It earned a gold certification from the Australian Recording Industry Association (ARIA), denoting shipments of 35,000 copies. In New Zealand, the song entered the singles chart at number 39 on the week ending January 2, 2006. Six weeks later, the song peaked at the top of the chart, where it remained for one month. "Run It!" entered the Swiss Singles Chart at number twelve on the week ending February 12, 2006. In the next week, it peaked at number five and remained in the top ten for six consecutive weeks.
The music video for "Run It!" was released on August 8, 2005. Directed by Erik White, it portrays an underground dance inside a school gym, where Brown meets a girl (Destiny Lightsy) that he is suddenly attracted to and with whom he wants to dance. The video features several dance sequences in which the males and females dance off against each other. During the sequences, Brown makes several movements toward his love interest. At the end, Brown and his love interest are about to kiss before the security guards arrive, and the whole gym is evacuated, with both of them pulled in separate directions. However, as soon as the guards find nobody there, they start dancing. The music video received two nominations at the 2006 MTV Video Music Awards for "Best New Artist" and "Viewer's Choice", but lost to Avenged Sevenfold's "Bat Country" and Fall Out Boy's "Dance, Dance".